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A Study of CART-TnMUC1 in Patients With TnMUC1-Positive Advanced Cancers

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ClinicalTrials.gov Identifier: NCT04025216
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Tmunity Therapeutics

Brief Summary:
Multi-center, open-label, first in human Phase 1 study of the safety, tolerability, feasibility, and preliminary efficacy of the administration of genetically modified autologous T cells (CART-TnMUC1 cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen, TnMUC1 and activating the T cell (CART- TnMUC1 cells).

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Ovarian Cancer Fallopian Tube Cancer Triple Negative Breast Cancer Multiple Myeloma Pancreatic Ductal Adenocarcinoma Biological: CART-TnMUC1 Drug: Cyclophosphamide Drug: Fludarabine Phase 1

Detailed Description:

The study is comprised of two parallel Phase 1 Arms (solid tumors and multiple myeloma) and a Phase 1a expansion in patients with TnMUC1+ platinum-resistant ovarian cancer.

The Phase 1 portion of the study is designed to identify the dose and regimen of CART-TnMUC1 cells that can be safely administered intravenously following the lymphodepletion regimen to patients with (1) advanced TnMUC1+ solid tumors or (2) advanced TnMUC1+ multiple myeloma in a parallel two-arm Phase 1 dose escalation study. It is anticipated that approximately 40 patients will enroll in the Phase 1 dose escalation.

The Phase 1a expansion portion of the study is a single arm study designed to assess the preliminary efficacy of CART-TnMUC1 cells administered intravenously following the lymphodepletion regimen to patients with TnMUC1+ platinum-resistant ovarian cancer. It is anticipated that approximately 40 patients will enroll in the Phase 1a expansion.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Parallel arms with sequential dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label, Multi-Center First in Human Study of TnMUC1-Targeted Genetically-Modified Chimeric Antigen Receptor T Cells in Patients With Advanced TnMUC1-Positive Solid Tumors and Multiple Myeloma
Actual Study Start Date : October 10, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : July 31, 2034


Arm Intervention/treatment
Experimental: Dose Escalation Arm1: Solid Tumors
Intravenous CART-TnMUC1 cells for patients with TnMUC1+ treatment-resistant ovarian cancer (including cancers of the fallopian tube), pancreatic ductal adenocarcinoma, hormone receptor (HR)-negative and human epidermal growth factor receptor 2 (HER2)-negative (triple negative) breast cancer and non-small cell lung cancer
Biological: CART-TnMUC1
Single intravenous administration of genetically modified autologous T cells engineered to express a TnMUC1-Targeted Genetically-Modified Chimeric Antigen (CAR)

Drug: Cyclophosphamide
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Drug: Fludarabine
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Experimental: Dose Escalation Arm 2: Multiple Myeloma
Intravenous CART-TnMUC1 cells for patients with TnMUC1+ relapsed/refractory multiple myeloma
Biological: CART-TnMUC1
Single intravenous administration of genetically modified autologous T cells engineered to express a TnMUC1-Targeted Genetically-Modified Chimeric Antigen (CAR)

Drug: Cyclophosphamide
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Drug: Fludarabine
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1




Primary Outcome Measures :
  1. Phase 1: Dose Identification of CART-TnMUC1 [ Time Frame: Up to 2 years ]
    Incidence of Dose Limiting Toxicity (DLT) in Arm 1 and Arm 2 cohorts

  2. Phase 1a Expansion: Objective Response in platinum-resistant ovarian cancer [ Time Frame: Up to 2 years ]
    Proportion of patients having a confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1


Secondary Outcome Measures :
  1. Safety of CART-TnMUC1 [ Time Frame: Up to 2 years ]
    Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and by severity Grade

  2. Tolerability of CART-TnMUC1 [ Time Frame: Up to 2 years ]
    Frequency of treatment emergent AEs, frequency of clinical changes from baseline in vital signs, changes in electrocardiogram, and hematology and chemistry laboratory shifts from baseline

  3. Feasibility of CART-TnMUC1 [ Time Frame: Up to 2 years ]
    Proportion of enrolled patients who did not receive CART-TnMUC1 cells

  4. Preliminary anti-tumor efficacy of CART as assessed by Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS as defined by the interval between CART-TnMUC1 cell infusion and date of death by any cause

  5. Preliminary anti-tumor efficacy of CART as assessed by Progression Free Survival (PFS) [ Time Frame: Up to 2 years ]
    PFS as defined by the interval between CART-TnMUC1 cell infusion and date of disease progression or death

  6. Preliminary anti-tumor efficacy of CART as assessed by Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    Proportion of patients having a confirmed CR or PR per RECIST v1.1

  7. Preliminary anti-tumor efficacy of CART as assessed by Clinical Benefit Rate [ Time Frame: Up to 2 years ]
    Proportion of patients having a confirmed CR, PR, or Stable Disease (SD) per RECIST v1.1

  8. Preliminary anti-tumor efficacy of CART as assessed by Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    DOR as defined by the interval between first documented CR or PR until first documented disease progression or death

  9. Preliminary anti-tumor efficacy of CART as assessed by Time to Response [ Time Frame: Up to 2 years ]
    Time to Response as defined by the interval between CART-TnMUC1 cell infusion and first documented CR or PR

  10. Expression of TnMUC1 [ Time Frame: Up to 15 years ]
    Correlation of the expression level of TnMUC1 with efficacy parameters

  11. Peripheral expansion and persistence of CART-TnMUC1 cells [ Time Frame: Up to 15 years ]
    Correlation with related efficacy and safety parameters



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Confirmed diagnosis of metastatic treatment-resistant ovarian cancer (including cancers of the fallopian tube), pancreatic adenocarcinoma, hormone receptor (HR)-negative and HER2-negative (triple negative) breast cancer (TNBC) or non-small cell lung cancer (NSCLC), or relapsed/refractory multiple myeloma
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Prior therapies as defined by tumor type: Multiple myeloma: relapsed or refractory disease previously treated with at least three different lines of therapy; NSCLC: received standard therapy including both checkpoint inhibition and platinum-based chemotherapy; Pancreatic adenocarcinoma: disease progression following at least one standard of care systemic chemotherapy; TNBC: disease progression following at least one prior systemic anti-cancer therapy regimen; patients with PD-L1-positive disease must have received a PD-L1 or PD-1 pathway inhibitor; Ovarian: platinum-resistant and must have received at least two lines of therapy for metastatic disease
  • Evaluable disease as defined by tumor type
  • TnMUC1+ disease, determined by centrally tested TnMUC1 expression in a prior or archival tumor biopsy
  • Completed prior anti-cancer therapy at least 2 weeks prior to Screening and toxicities from any previous therapy must have recovered to grade 1 or 0
  • Life expectancy greater than 3 months
  • Serum creatinine ≤ 1.2 mg/dL or calculated creatinine clearance ≥ 60 ml/min (using the Cockcroft-Gault formula)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper institutional limit of normal with the following exception: Patients with known hepatic metastases, AST or ALT ≤ 3 x upper institutional limit of normal
  • Serum total bilirubin < 1.5 mg/dL with the following exception: patients with known Gilbert's disease, serum total bilirubin < 3 mg/dL
  • Serum albumin ≥ 3.0 g/dL (solid tumor patients in Arm 1 and Phase 1a only, not applicable to patients with multiple myeloma)
  • Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 8 weeks of screening
  • Hemoglobin ≥ 9 g/dL
  • Absolute neutrophil count ≥ 1500/μL
  • Platelet count ≥ 100,000/μL (≥ 30,000/μL if bone marrow plasma cells are ≥ 50% of cellularity for myeloma patients)
  • Absolute lymphocyte count of > 500/μL

Key Exclusion Criteria:

  • Active invasive cancer other than the proposed cancers included in the study
  • Current treatment with systemic high-dose corticosteroids (defined as a dose greater than the equivalent of prednisone 20 mg/day)
  • Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or have a history of severe autoimmune disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy should have been stopped within 6 weeks prior to screening visit)
  • Current, active human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) infections
  • Prior allogeneic stem cell transplant
  • Active and untreated central nervous system (CNS) malignancy
  • History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients that would preclude the patient safely receiving CART-TnMUC1 cells
  • Active or recent (within the past 6 months prior to apheresis) cardiac disease, defined as (1) New York Heart Association (NYHA) Class III or IV heart failure, (2) unstable angina or (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias
  • Have inadequate venous access for or contraindications for the apheresis procedure
  • Pregnant or breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04025216


Contacts
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Contact: Karen Chagin, MD 215-966-1472 clinicaltrials@tmunity.com

Locations
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United States, California
The Angeles Clinic and Research Institute Recruiting
Los Angeles, California, United States, 90025
Contact: Omid Hamid, MD    310-231-2181    smukarram@theangelesclinic.org   
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Alfred Garfall, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Sponsors and Collaborators
Tmunity Therapeutics

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Responsible Party: Tmunity Therapeutics
ClinicalTrials.gov Identifier: NCT04025216     History of Changes
Other Study ID Numbers: CART-TnMUC1-01
First Posted: July 18, 2019    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tmunity Therapeutics:
Chimeric Antigen Receptor (CAR)
T-cells
TnMUC1
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Adenocarcinoma
Fallopian Tube Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fludarabine